Psychiatric disturbances and mental health issues arising during treatment with second line anti-tuberculosis medication

1. Psychiatricdisturbances and mental health issuesarising during treatment with second line anti-tuberculosis medications Module 13

2. Psychiatric Disturbances and MDR-TB • Level of psychiatric disorders • Borderline Disorders Whose appearance originates from somatic, psychological and intoxication factors. • PsychoticDisorders Whose origincan beof an intra-infectious, pharmacogenic,andcomorbidetiology.

3. Psychiatric Disturbances and MDR-TB • Borderline Disorders • Asthenic Syndrome • Depressive Syndrome • Hypochondriacal Syndrome • Phobic Syndrome • Paranoiac Syndrome

4. Psychiatric Disturbances and MDR-TB • Psychotic Disorders Acute,lastingfrom a few hours up to2-3 days (delirium syndrome, amentia, oneiroid syndrome, verbal hallucination and twilight state) Protracted, lasting from 2 weeks to 2 months. (confabulation,transitory Korsakoff’s syndrome, pseudo-paralytic syndrome, episode of depression, depression-delirium disorder, maniacal syndrome, hallucinatory-paranoid disorder, apathetic stupor) Chronic, lasting more than 2 months. Personality change of organic type, psycho- organic syndrome, dementia)

5. Psychiatric Disturbances and MDR-TB • PsychoticDisorders • Initial Psychosis – endogenicpsychiatric disorders (schizophrenia, manic-depressive psychosisand others) emerging against a background of somatogenesis and intoxication. • Intra-infectious Psychosis – psychotic syndromes, emerging at the height of the infectious process,and originating from infectious disease. In these casespsychiatric disordersare observed against a background of elevated temperature and other symptoms of acute infectious process. Acute psychotic syndromespass simultaneously with a fall in temperature and decreasing signs of infectious intoxication. • Pharmacogenic Psychosis – acute psychotic disorders, emerging in response to medication use.

6. Psychiatric Disturbances and MDR-TB • Complicationsin managing psychiatric disorders: • Risk of poor treatment outcome • Worsening quality of life for patient • Emotional stress for the attending physician

7. Psychiatric Disturbances and MDR-TB Risk of poor treatment outcome • Poor adherence to treatment by the patient or treatment default. • Stopping medications, due to the development of side effects.

8. Psychiatric Disturbances and MDR-TB • In the case of untimely diagnosis and treatment, psychiatric disorders can lead to unfavorable outcomes: treatment failure, default, or even death. • Managing psychiatric disorders in a timely manner is a crucial element of a DOTS-Plus program.

9. Survey of Literature Psychiatric complications, arising during anti-tuberculosis treatment, have been observed since the 1950s. • Isoniazid • Cycloserine • Ethionamide • Ethambutol • Fluoroquinolones

10. Isoniazid • Encountered in approximately 2.0% of cases • Symptoms include depression, increased irritability, obsessive neurosis, psychosis, attempts at suicide • Inhibits MAO (monoamine oxidase) and/or decreases the production of norepinephrine, serotonin, dopamine and gamma-aminobutyl acid as a result of pyridoxine deficiency. • Side effects can occur on average four weeks after the start of treatment.

11. Isoniazid • Risk Factors: • Dosage > 5 mg/kg • Age > 50 • Comorbid pathology: diabetes, alcoholism, hypothyroidism, psychiatric disease/disorder in medical history

12. Cycloserine • 9.7% - 50% of all patients receive Cycloserine • Probably owing to a decrease in the production of gamma-aminobutyl acid in the CNS • Changes occur within the first months of treatment • These include psychosis, depression, hallucinations, irritability, euphoria, attempts at suicide

13. Cycloserine • Risk Factors: • Level of Cycloserine in blood exceeding the permissible therapeutic concentration • Simultaneously receiving doses of ethionamide, isoniazid and fluoroquinolones • Ethanol intake

14. Ethionamide • Cases of depression, feelings of fear/anxiety, psychosis and suicide attempts have been noted • Mechanism similar to that of Isoniazid

15. Ethambutol • Cases of mania, confusion, and psychosis have been described • There is insufficient data regarding the mechanism of action

16. Fluoroquinolones • Cases of psychosis, depression, delirium and nightmares have been described • Encountered in ~ 0.7%cases • In elderly patients: delirium, paranoid disorders • In young patients: depression, mania • Risk factors: liver or kidney disease, simultaneously taking other antibiotics or immunodepressants, preexisting psychiatric disorders or the presence of psychological-social stress factor

17. Psychological-social stress factors and MDR-TB A high level of depression, feelings of fear/anxiety and suicidal tendencies can be present toward the beginning of chemotherapy

18. Psychological-social stress factors and MDR-TB • Social Stigma • Feelings of guilt at the possibility of infecting those around you with the disease • Socioeconomic and psychological complexity of the illness • Increased dependence and the loss of social standing, decreased role in family • Complexity of achieving a favorable outcome with MDR-TB and physical suffering • Death of those close to you • Poverty

19. Overview of the Project in Tomsk • The present research was carried out at a Tuberculosis Hospital located within the structure of the Tomsk Oblast Penitentiary System. Since September of 2000 the DOTS-Plus program has been clinically implemented here. • 118 patients (all men) with poly-resistant pulmonary tuberculosis were under observation.

20. Overview of the Project in Tomsk Goal of this research: • Preventing the emergence of psychiatric disorders (first of all those of a psychotic level) • Development andimplementation ofcomprehensive approaches in the treatment of psychological changes, emerging during therapy with second-line TB medications, taking into account the psychiatric status of the patient.

21. Overview of the Project in Tomsk • Significance of the Problem Medications used for treating multi-drug resistant tuberculosis(second-line antibiotic medications) possess marked neurotropic activity, which for its own part accounts for a high percent of secondary disorders.

22. Overview of the Project in Tomsk • METHODS • Clinical-psychopathological tests were conducted in accordance with the requirements of the International Disease Classification (IDC – 10). • For the study of patients’ psychological status the following methods were employed: SMPE (Standardized Method of Personality Examination), LNP (Level of Neurotization and Psychopathization) andprojecting method- Hand-Test.

23. Problems existing prior to disease in those patients who suffer from MDR-TB and are receiving treatment through the DOTS-Plus Program Characteristics at the Beginning of Treatment

24. Psychiatric Disorders

25. Psychiatric Disorders • Onset of Schizophrenia • Suicide • Spasmodicparoxysm • Suicideattempt (failed) • Acute psychosis • Episode of Depression • Asthenic Syndrome

26. Morbidityand Incidenceof Psychiatric Illness Among Patients with MDR-TB, Lima (Peru)

27. Methods of Correcting Psychiatric Side Effects Neurotic Level: - psychocorrection, - tranquilizer of the benzodiazepine line (Elinium, Relanium, Seduxen, Sibason). Affected disorders: - psychocorrection, - tranquilizer of the benzodiazepine line (Elinium, Relanium, Seduxen, Sibason). • tricyclic antidepressants (Amitriptiline, Coaxil). • Antidepressants with a selective effect on serotonin metabolism: Sertraline (Zoloft), Prozac (Fluoxetine)

28. Methods of Correcting Psychiatric Side Effects Acute Symptomatic Psychosis: -Detoxification therapy; -В group vitamins, hepatoprotectors, antioxidants,Nootropics; -tranquilizers,principally those witha sedative pattern of action; -neurolepticswitha sedative pattern of action (used when tranquilizers are ineffective). ProtractedSymptomatic Psychosis : -Tranquilizers; -“lesser” neuroleptics with a selective pattern of action; - witha sedative pattern of action (used when tranquilizers are ineffective). - when necessary for prolonged forms: neurolepticswitha sedative pattern of action - “lesser” antidepressants; - “greater” antidepressants (if “lesser” are ineffective);

29. Treatment Strategy, Lima, Peru • Support from the Social Worker • Observation • Prescription of psychotropic medications • Psychotropic therapy • Galdol orRisperidone to cope with psychoses • Inhibitors of Serotonine receptors with depression • Benzodiazepines of short or medium effect • Psychotherapy • Permanentcessation of Cycloserinewas not implemented

30. Conclusions • TB treatment with second-line antibiotics causes symptomatic psychiatric disorders, both of neurotic and psychotic amplitude • The degree and frequency of symptomatic psychiatric disorder occurrence is preconditioned by a variety of factors: somatic aggravation, toxic effects on CNS related to TB pathology, pharmacogenic factors, and to some extent the intoxicating activity of Cycloserine and pre-disease background. • The suggested comprehensive methods for correcting psychological disturbances (psychotropic therapy, pathogenic therapy, cognitive psychotherapy and dynamic observation of psychological climate within the group), have permitted continued inclusion of all patients in the program, and their continued treatment with anti-tuberculosis medications.

31. Clinical Example: Psychosis Patient B, age 34, receivingDOTS-Plus treatment, At the end of the second month of treatment the patient’s behavior changed abruptly.He claimed that he wasthe “right hand man” of a famous “master thief” and demanded the corresponding privileges. He claimed that a conspiracy was being hatched against him, he “saw”how everyone was shadowing him. Additionally he claimed that devices had been installed within the TB drugs by which the psychiatrist could read his thoughts and exert pressure him.As a result of this he categorically refused further treatment with anti-tuberculosis therapy.

32. Clinical Example: Psychosis • Patient was placed in a ward for “acute conditions,” where he was provided with around-the-clock supervision. • Therapy withTB drugs was temporarily suspended. • Comprehensive therapy was conducted: detoxification, B group vitamins, hepatoprotectors , antioxidants, nootropics, and a neuroleptic with selective effect (galoperidol).

33. Clinical Example: Psychosis • With the implementation of therapy psychotic symptoms were reduced, the patient became skeptical of his own delusions arising during his psychotic episode. Anti-tuberculosis treatment was restarted. • Subsequently this patient’s psychotic condition evolved again, which required the use of selected neuroleptics with prolonged action (Galoperidol Dec.), which he received until the end of his TB treatment.